Involvement of spinal NMDA receptors in capsaicin-induced nociception.
Intraplantar injection of capsaicin into the mouse hindpaw produced an acute nociceptive response. The involvement of N-methyl-D-aspartate (NMDA) receptors was examined by intrathecal administration of various excitatory amino acid (EAA) receptor antagonists. The selective and competitive NMDA receptor antagonists, D(-)-2-amino-5-phosphono-valeric acid (APV) and (+/-)-3-(2-carboxypiperazin-4-yl) propyl-1-phosphoric acid (CPP), were most potent in inhibiting the nociceptive response induced by capsaicin (ED50, 0.23 nmol and 0.12 nmol). The noncompetitive NMDA receptor antagonist dizocilpine (MK-801) and the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) had similar effects on the capsaicin-induced nociception (ED50, 2.90 and 7.98 nmol), while ketamine and 7-chlorokynurenic acid were without effect. Ifenprodil, an antagonist at the receptor-coupled polyamine site, showed a significant reduction of the nociceptive response (ED50, 13.8 nmol). The inhibitory effects of APV, CPP, MK-801, and ifenprodil were reversed by co-administration of NMDA. Coadministration of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) or kainate resulted in a marked reduction of CNQX-induced antinociception. The present results suggest that the NMDA receptor plays a key role in spinal nociceptive processing as measured by the capsaicin test in mice. This nociceptive test may be useful for evaluating competitive NMDA antagonists.
Sakurada
T
T
Department of Biochemistry, Daiichi College of Pharmaceutical Sciences, Fukuoka, Japan.
Wako
K
K
Sugiyama
A
A
Sakurada
C
C
Tan-No
K
K
Kisara
K
K
D000818:Animals; D002211:Capsaicin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D002211:Capsaicin